PROTECTIVE EFFECT OF AMILORIDE AGAINST REPERFUSION DAMAGE AS EVIDENCED BY INHIBITION OF ACCUMULATION OF FREE FATTY-ACIDS IN WORKING RAT HEARTS

To examine whether amiloride protects against ischemia-induced or repe rfusion-induced damage to the heart, mechanical and metabolic studies were performed in the isolated, working rat heart. Ischemia decreased both mechanical function and the tissue levels of high-energy phosphat es and increased the tissue levels of free fatty acids (FFAs). Reperfu sion restored the levels of high-energy phosphates but further increas ed FFA accumulation. For this reason, accumulation of FFAs was used as an indicator of both ischemia-induced and reperfusion-induced damage. Drugs were added to the perfusion solution 5 min before ischemia unti l the end of ischemia (pre) or until 10 min after reperfusion (pre+pos t). Diltiazem (1 or 5 mu mol/L pre) decreased the mechanical function of the non-ischemic heart and attenuated both ischemia-induced and rep erfusion-induced accumulation of FFAs. Amiloride (50 mu mol/L pre) did not affect the mechanical function of the non-ischemic heart or atten uate ischemia-induced or reperfusion-induced FFA accumulation effectiv ely. However, amiloride (50 mu mol/L pre+post) did markedly attenuate the reperfusion-induced accumulation of FFAs. In conclusion, diltiazem attenuates both ischemia-induced and reperfusion-induced myocardial d amage, probably through its energy-sparing effect as a result of a dec rease in mechanical function before ischemia. In contrast, amiloride a ttenuates only the reperfusion-induced myocardial damage through mecha nisms other than the energy-sparing effect.